Hepatotoxicity of brominated benzenes: relationship between chemical structure and hepatotoxic effects in acute intoxication of mice.
Brominated benzenes appear in the environment and human tissues. Their detection in the environment may be as a result of their usage, e.g. hexabromobenzene (HBB), and as products of HBB degradation or metabolism. The aim of this study was to compare liver impairment in acute intoxication of mice with bromobenzene (BB), 1,2,4-tribromobenzene (1,2,4-triBB), 1,3,5-tribromobenzene (1,3,5-triBB), 1,2,4,5-tetrabromobenzene (1,2,4,5-tetraBB) and hexabromobenzene (HBB). The data for these compounds were compared with the data obtained for dibromobenzenes (1,2-dBB, 1,3-dBB, 1,4-dBB). Male Balbc mice were administered the investigated compounds in single, intraperitoneal doses equal to 20-90% of the approximate lethal dose (ALD). Acute toxicity of bromobenzenes decreases with the increase of the number of bromine atoms in the molecule. All examined compounds decreased the liver glutathione (GSH) level in a short time following administration. Later in the experiment, GSH either returned to control values or the concentration increased. Changes in alanine aminotransferase (ALT) activity in mice serum depended on the type of compound and the time of observation. BB, 1,2-dBB, 1,3-dBB and 1,2,4-triBB caused statistically significant increases (30- to 120-fold) in ALT activity. For the remaining compounds these changes were not significant being two- to threefold. Histopathological examination demonstrated that BB, 1,2-dBB, 1,3-dBB and 1,2,4-triBB resulted in coagulative or haemorrhagic necrosis in the liver central lobular zone. All investigated compounds resulted in the increase of gamma-glutamyltransferase activity in serum and malondialdehyde concentration in liver. Octanol water partition coefficient (expressed as log P) and molecular volume (log V) were calculated for all examined compounds. With the increase of lipophilicity and molecule size, the ability of the examined compounds to decrease the level of GSH in mice liver and increase ALT activity in the serum diminishes.
Szymańska
J A
JA
Department of Toxicological Chemistry, School of Pharmacy, Medical University of Lódź, Poland.
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001555:Benzene Derivatives / Q000737:chemistry / Q000633:toxicity; D001969:Bromobenzenes / Q000737:chemistry / Q000633:toxicity*; D005978:Glutathione / Q000032:analysis* / Q000097:blood; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D013329:Structure-Activity Relationship; D005723:gamma-Glutamyltransferase / Q000097:blood
D001555:Benzene Derivatives; D001969:Bromobenzenes; C102880:1,3-dibromobenzene; C102879:1,2-dibromobenzene; C026924:1,2,4-tribromobenzene; C055383:1,3,5-tribromobenzene; C110818:1,2,4,5-tetrabromobenzene; C066656:1,4-dibromobenzene; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D005978:Glutathione; C017363:hexabromobenzene